The immune system is comprised of many different cell types, biomolecules and organs. These include lymphocytes, monocytes and polymorphonuclear leukocytes, numerous soluble chemical mediators (cytokines and growth factors), the thymus, postnatal bone marrow, lymph nodes, liver and spleen. All of these components work together through a complex communication system to fight against microbial invaders such as bacteria, viruses, fungi and parasites, and tumor cells. Together, these components recognize specific molecular antigens as foreign or otherwise threatening, and initiate an immune response against cells or viruses that contain the foreign antigen. The immune system also functions to eliminate damaged or cancerous cells through active surveillance using the same mechanisms used to recognize microbial or viral invaders. The immune system recognizes the damaged or cancerous cells via antigens that are not strictly foreign, but are aberrantly expressed or mutated in the targeted cells.
The human prostatic acid phosphatase (PAP) is predominantly expressed in the prostate gland. Elevated serum levels of PAP are often observed in patients with prostate cancer or other prostate conditions, with the highest serum levels of PAP found in patients with metastasized prostate cancer. (Kirchenbaum Annals. of the New York Academy of Sciences 1237 (2011) 64-70). PAP expression is also observed at very low levels in a limited set of normal, non-prostate tissues (including pancreatic islet cells and pilosebaceous units of the skin), as well as in other tumor settings (including breast and colon). The level of PAP expression in these tissues can be at least 1-2 orders of magnitude lower than that detected in the prostate of patients with prostate cancer or another prostate condition. (Graddis et al., Prostatic acid phosphatase expression in human tissues. Int J Clin Exp Pathol. 2011 March 31; 4(3): 295-306).
Over 95% of prostate cancer cells express PAP. Therefore several immunotherapeutic strategies for prostate cancer have been devised using PAP as a target. For instance, Cancer Biology and Therapy (March 2005, vol. 4, issue 3) reports promising results from a clinical study in which a patient's own immune cells were collected, stimulated to become immunoreactive to PAP, and then returned to the patient by intravenous injection. These new immunological approaches rely on methods that can effectively induce a PAP-specific immunity, including T cell-mediated immunity.
One consequence of an effective immunotherapy may be antigen spread which can result from tumor cell death during the initial response to an immunotherapy which can lead to the release of tumor-associated antigens and the priming of self-reactive T and/or B lymphocytes specific to these antigens. Antigen spread can subsequently promote more efficient tumor killing and can occur with a higher frequency in clinical responders, therefore providing avenues for the identification of novel, mechanism-based, biomarkers of clinical outcome. See, e.g., Ribas, A. et al., Determinant spreading and tumor responses after peptide-based cancer immunotherapy. Trends Immunol, 24, 58-61 (2003).